
Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)
Опубликована: Дек. 18, 2024
Extracellular vesicles (EVs) and extruded nanovesicles (ENVs) are promising (NVs) for drug delivery. However, the application of these NVs is strongly hindered by their short half-life in circulation. Macrophages (Mφs) liver spleen contribute to rapid depletion NVs, but underlying mechanism unclear. By collecting supernatant PANC-1 cells squeezing cells, EVs ENVs derived from were prepared via ultracentrifugation. subsequently identified western blot, particle size measurement, electron microscopy. The distribution mouse bodies was observed with a live animal imaging system. Liver Mφs extracted isolated after administered, transcriptome profiling applied determine differentially expressed genes (DEGs). siRNAs targeting interested designed synthesized. In vitro experiments, transfected siRNA or treated corresponding inhibitor, which NV uptake recorded. Doxorubicin (DOX) encapsulated using an ultrasound method. cell-derived tumors established nude mice vivo, inhibitor pretreatment no treatment administered before intravenous injection ENVs-DOX, therapeutic efficacy ENVs-DOX evaluated. first identified. After injection, most engulfed spleen. Seven interest selected sequencing validated RT‒PCR. These results confirmed that TLR2 signaling pathway responsible phagocytosis. siTLR2 its sparstolonin B (SpB) significantly inhibited internalization downregulated activity pathway. accumulation vivo SpB 40 min ultimately delaying tumor progression. plays crucial role sequestration Mφs. A novel antiphagocytic strategy inhibits clearance prolongs thereby improving delivery efficiency,
Язык: Английский